Ethyl Acetate → 2-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acid

HRID 62524

Reaction equation

HRID 62524 reaction equation
[Cl:1][C:2]1[C:3]([NH:17][C:18]2C=[CH:24][CH:23]=[CH:22][C:19]=2C#N)=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH2:14][CH3:15])[N:12]=[C:11]([CH3:16])[CH:10]=2)=[N:6][CH:7]=1.[OH-].[Na+].[C:28]([O:31]CC)(=[O:30])[CH3:29]>O1CCOCC1>[Cl:1][C:2]1[C:3]([NH:17][C:18]2[CH:19]=[CH:22][CH:23]=[CH:24][C:29]=2[C:28]([OH:31])=[O:30])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH2:14][CH3:15])[N:12]=[C:11]([CH3:16])[CH:10]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 593144512-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzonitrile

Product 1

HCID 593144602-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acidYield 66.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a 50 mL round bottom flask was added 2-({5-chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzonitrile (300 mg, 0.850 mmol), and NaOH 1 M solution (10 ml, 10.00 mmol) in 1,4-dioxane (10 mL). The mixture was heated under reflux for 18 hours. Ethyl acetate was added (20 mL) and the layers separated—all product stayed in the water phase. The water phase was neutralized with 6 N HCl, and 40 mL of ethyl acetate were added. The organic layer was separated, washed with brine, dried over MgSO4, filtered and evaporated. 2-({5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acid (220 mg, 0.562 mmol, 66.1% yield) was isolated as off-white solid and used in the next step without further purification. LCMS (M+H)+=372.1; 1H NMR (400 MHz, MeOD) ppm 1.33 (t, J=7.20 Hz, 4 H) 2.22 (s, 3 H) 4.00 (q, J=7.33 Hz, 2 H) 6.01 (s, 1 H) 6.82 (s, 1 H) 7.06 (td, J=7.52, 1.14 Hz, 1 H) 7.39-7.49 (m, 1 H) 7.49-7.55 (m, 1 H) 7.87-7.94 (m, 1 H) 8.05 (dd, J=7.83, 1.52 Hz, 1 H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 18 hours
  3. customthe layers separated—all product
  4. additionwere added
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-7395ac6ead584d759c88f6bfcdf97af7
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Linked notes

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